A variety of medical devices have been designed for use within a patient's body. Many such devices are surgically implanted and remain in the body for extended periods. Not surprisingly, the biocompatibility of the material used in these devices is a significant issue. The literature contains examples of methods and compositions designed to improve the biocompatibility, and particularly the hemocompatibility, of medical devices. These include attempts to reduce the formation of thromboses by modifying a surface of the device so that it contains anti-thrombotic agents. In addition, medical devices comprising ultra-smooth pyrolytic carbon, which is typically more biocompatible than devices made of inorganic materials or ceramics, is familiar to those of skill in the art and are described, for example, in U.S. Pat. No. 7,632,309.
While medical devices, and particularly cardiovascular prostheses, generally provide important clinical benefits, patients receiving these devices, including those devices comprised of pyrolytic carbon, typically must receive long term anticoagulant therapy. Such anticoagulant therapy may cause inconvenience to patients and adversely affect the quality of their lives. This is especially true for those who are in developing countries, where coagulation monitoring is not a standard care that is available in most of the clinics or hospitals. The cost of medication can also be an issue. Moreover, systemic administration of anticoagulants can produce hemorrhagic complications in patients at high risk of bleeding, including intracranial hemorrhage. Thus, alternative means for decreasing the risk of thromboses after post-surgical implantation of medical devices is desired.
Medical devices incorporating means to increase levels of nitric oxide (NO) in vivo after surgical implantation are also known. These are thought to work by increasing the thrombo-resistance of the device. See, for example, U.S. Pat. No. 7,128,904; U.S. Patent Application Publication No. 2007/0014829; U.S. Patent Application Publication No. 20090287072; Yang et al., Langmuir 2008, 24, 10265-10272; and Hwang and Meyerhoff, Biomaterials 2008, 29, 2443-2452. NO is a naturally occurring species that is generated by the endothelial cell (EC) layer that lines all blood vessels, and greatly contributes to the natural thromboresistance of the inner wall of healthy blood vessels. On the EC layer and/or (in some cases) within the blood, naturally occurring copper- and/or selenium-containing membrane proteins serve as catalysts to convert endogenous NO precursors (i.e., nitrosothial species (RSNO)) into the potent antiplatelet-agent NO. The nitrosothials are reported to be present in blood and other physiological fluids, where they are regenerated by the body via biological reactions, thereby maintaining their physiological basal levels.
U.S. Patent Application Publication No. 2009/0287072 specifically describes biocompatible, thrombo-resistant coatings for medical devices comprising the use of chalcogenide compounds as NO generators. There currently remains, however, a need for additional means to achieve an increase in biocompatibility, and particularly hemocompatability, of surgically implantable medical devices.